title: Zebrafish and mouse TASK-2 K(+) channels are inhibited by increased CO2 and intracellular acidification.
abstract: TASK-2 is a K2P K(+) channel considered as a candidate to mediate CO2 sensing in central chemosensory neurons in mouse. Neuroepithelial cells in zebrafish gills sense CO2 levels through an unidentified K2P K(+) channel. We have now obtained zfTASK-2 from zebrafish gill tissue that is 49 % identical to mTASK-2. Like its mouse equivalent, it is gated both by extra- and intracellular pH being activated by alkalinization and inhibited by acidification. The pHi dependence of zfTASK-2 is similar to that of mTASK-2, with pK 1/2 values of 7.9 and 8.0, respectively, but pHo dependence occurs with a pK 1/2 of 8.8 (8.0 for mTASK-2) in line with the relatively alkaline plasma pH found in fish. Increasing CO2 led to a rapid, concentration-dependent (IC50 ~1.5 % CO2) inhibition of mouse and zfTASK-2 that could be resolved into an inhibition by intracellular acidification and a CO2 effect independent of pHi change. Indeed a CO2 effect persisted despite using strongly buffered intracellular solutions abolishing any change in pHi, was present in TASK-2-K245A mutant insensitive to pHi, and also under carbonic anhydrase inhibition. The mechanism by which TASK-2 senses CO2 is unknown but requires the presence of the 245-273 stretch of amino acids in the C terminus that comprises numerous basic amino acids and is important in TASK-2 G protein subunit binding and regulation of the channel. The described CO2 effect might be of importance in the eventual roles played by TASK-2 in chemoreception in mouse and zebrafish.
authors.affiliation: Centro de Estudios Científicos (CECs), Avenida Arturo Prat 514, Valdivia, Chile.
authors.forename: Gaspar
authors.initials: G
authors.lastname: Peña-Münzenmayer
authors.forename: María Isabel
authors.initials: MI
authors.lastname: Niemeyer
authors.forename: Francisco V
authors.initials: FV
authors.lastname: Sepúlveda
authors.forename: L Pablo
authors.initials: LP
authors.lastname: Cid
mesh_terms: D000200:Action Potentials; D000595:Amino Acid Sequence; D000818:Animals; D002245:Carbon Dioxide / Q000378:metabolism* / Q000494:pharmacology; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology; D005880:Gills / Q000166:cytology / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D024683:Potassium Channels, Tandem Pore Domain / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D002257:Carbonic Anhydrase Inhibitors; C498739:Kcnk5 protein, mouse; D024683:Potassium Channels, Tandem Pore Domain; D029961:Zebrafish Proteins; C000595369:kcnk5a protein, zebrafish; D002245:Carbon Dioxide